The negative inotropic effect of beta3-adrenoceptor stimulation in the beating guinea pig heart

J Cardiovasc Pharmacol. 2000 May;35(5):786-90. doi: 10.1097/00005344-200005000-00016.


Although beta3-adrenoceptors (ARs) have been extensively characterized in brown and white adipocytes, their actions in the beating heart are unclear. We examined the effects of a beta3-AR agonist, BRL37344, on cardiac function and calcium transients in Langendorff-perfused guinea pig hearts by simultaneously measuring left ventricular (LV) pressure and Ca2+-dependent indo-1 fluorescence. BRL37344 induced a dose-dependent negative inotropic effect at concentrations from 10(-11) to 10(-8) M. Maximally, LV developed pressure decreased to 80+/-2%, +dP/dt to 81+/-2%. and -dP/dt to 81+/-3% of their respective control values (p < 0.01). The amplitude of the Ca2+ transient also decreased (to 92+/-3% of the control level; p < 0.01). The BRL37344 dose-response curve was not altered by nadolol (10(-5) M), a potent beta1- and beta2-AR antagonist, but completely suppressed by bupranolol (10(-6) M), a potent beta1-, beta2- and beta3-AR antagonist. To assess the potential role of a nitric oxide synthase (NOS) pathway, we determined whether the NOS inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), modified the contractile response to BRL37344. L-NAME (10(-7) and 10(-4) M) attenuated the negative inotropic effects on LV developed pressure by 35 and 50%, suggesting that beta3-AR stimulation induces a negative inotropic effect on guinea pig hearts partly through a decrease in the Ca2+ transient and partly by the NOS pathway.

MeSH terms

  • Adrenergic beta-Agonists / pharmacology*
  • Animals
  • Calcium / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Ethanolamines / pharmacology*
  • Guinea Pigs
  • Heart / drug effects*
  • Male
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism
  • Receptors, Adrenergic, beta / metabolism*
  • Receptors, Adrenergic, beta-3
  • Ventricular Function, Left / drug effects


  • Adrenergic beta-Agonists
  • Enzyme Inhibitors
  • Ethanolamines
  • Receptors, Adrenergic, beta
  • Receptors, Adrenergic, beta-3
  • BRL 37344
  • Nitric Oxide Synthase
  • Calcium
  • NG-Nitroarginine Methyl Ester